The proposed research will investigate some of the basic physiological, morphological, and pharmacological properties of mammalian neurons and glia in an in vitro system. The well established guinea pig hippocampus tissue slice preparation will be used in most experiments and offers several advantages over in vivo experimentation on mammalian cortex, including ready access of perfusion solutions to the extracellular space, direct visualization of the anatomic organization of this region, and ease of intracellular recordings from neurons and glia. Using intracellular recording techniques, tissue perfusion, and in some cases K ion sensing microelectrodes, the following projects will be undertaken: 1) The ionic determinants of resting membrane potential in glial cells and neurons will be determined under normal conditions and for glial cells under conditions of reactive gliosis. 2) Morphological studies on both normal and reactive (presumed) glial cells using intracellular injections of horseradish peroxides will allow detailed morpho-physiological correlation. 3) The slow hyperpolarizing potential in glial cells which follows in the wake of intense neural activity will be characterized and its mechanism explored. 4) The response of glial cells to the application of the neurotransmitters GABA and acetylcholine will be investigated.